When proteins useful as pharmaceuticals are produced with the recombinant DNA technique, use of animal cells enables complicated post-translational modification and folding which prokaryotic cells can not perform. Therefore, animal cells are frequently used as host cells for producing recombinant proteins.
Recently, a large number of biopharmaceuticals, such as antibodies and physiologically active proteins, have been developed. Techniques that permit efficient production of recombinant proteins by animal cells lead to cost reduction of biopharmaceuticals and promise their stable supply to patients.
Under these circumstances, a method of protein production with higher production efficiency is desired.
An anion exchanger is a transporter that mediates antiport of intracellular and extracellular anions across a plasma membrane (membrane transport protein). An SLC4 family is a family of HCO3− transporters, and three members belonging to the SLC4 family, namely AE1, AE2, and AE3, have a function to exchange Cl− outside a plasma membrane for HCO3− inside a plasma membrane.
In a kidney, AE1 is found in a intercalated cells in collecting ducts in the basolateral membrane (Non-Patent Document 1). It has been known that mutations in human AE1 cause distal renal tubular acidosis (Non-Patent Documents 2 and 3).
Further, in a kidney, three isoforms of AE2, namely AE2a, AE2b, and AE2c, have been found. AE2 is considered to regulate intracellular pH homeostasis for cell signal transduction (Non-Patent Document 4). However, an AE2 knockout mouse that dies during the weaning period has been found to suffer no renal phenotypic abnormalities (Non-Patent Document 5).
An SLC26 is a relatively new anion exchanger family, and it has been suggested that a large number of its members (for example, SLC26A3, SLC26A4, SLC26A6, and SLC26A9) are bicarbonate exchangers (Non-Patent Documents 6 to 11).
On the other hand, it has been absolutely unknown that by strongly expressing an anion exchanger having a bicarbonate transporter function, uptake of anions into a cultured cell and excretion of anions to the outside of the cell, as mediated by the anion exchanger, can be artificially promoted, which contributes to improvement in the production of a desired recombinant protein in the cultured cell.
[Non-Patent Document 1]
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